Ultrastructural evidence for self-replication of alzheimer-associated Aβ42 amyloid along the sides of fibrils

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Bibtex

@article{aa1968c958274968b104ea108c3c33fc,
title = "Ultrastructural evidence for self-replication of alzheimer-associated Aβ42 amyloid along the sides of fibrils",
abstract = "The nucleation of Alzheimer-associated Aβ peptide monomers can be catalyzed by preexisting Aβ fibrils. This leads to autocatalytic amplification of aggregate mass and underlies self-replication and generation of toxic oligomers associated with several neurodegenerative diseases. However, the nature of the interactions between the monomeric species and the fibrils during this key process, and indeed the ultrastructural localization of the interaction sites have remained elusive. Here we used NMR and optical spectroscopy to identify conditions that enable the capture of transient species during the aggregation and secondary nucleation of the Aβ42 peptide. Cryo-electron microscopy (cryo-EM) images show that new aggregates protrude from the entire length of the progenitor fibril. These protrusions are morphologically distinct from the wellordered fibrils dominating at the end of the aggregation process. The data provide direct evidence that self-replication through secondary nucleation occurs along the sides of fibrils, which become heavily decorated under the current solution conditions (14 μM Aβ42, 20 mM sodium phosphate, 200 μM EDTA, pH 6.8).",
keywords = "Aggregation mechanism, Amyloidosis, Fibril formation, Neurodegeneration, Self-assembly",
author = "Mattias Tornquist and Risto Cukalevski and Ulrich Weininger and Georg Meisl and Knowles, {Tuomas P.J.} and Thom Leiding and Anders Malmendal and Mikael Akke and Sara Linse",
year = "2020",
month = may,
day = "26",
doi = "10.1073/pnas.1918481117",
language = "English",
volume = "117",
pages = "11265--11273",
journal = "Proceedings of the National Academy of Sciences",
issn = "1091-6490",
publisher = "National Acad Sciences",
number = "21",

}